The objective of the research projects in this application is to improve our understanding of the molecular pathways to thymic leukemia and lymphoma, and how these pathways interact. Many of the proposed I experiments involve manipulating gene expression in strains of mice, and exploring the consequences both in terms of alteration of expression of other genes and on the incidence and timing of thymic disease in the animals. It is anticipated that the results of these four projects will inform one another. Project results will be conveyed to other members of the program with the assistance of members of the Biostatistics Core. The Biostatistics Core will assist all the research projects contained in this program. The purpose of the Biostatistics Core, Core B, is to provide the following services that will be utilized by the research projects included in this Program Project. 1. To provide bioinformatics support for the computational discovery of transcription factor binding motifs from ChiP-chip experiments in Project 1. 2. To provide biostatistical collaboration for animal studies, including the laboratory components of those studies, for Projects 2, 3, and 4. This will include all aspects of the design and analysis of such studies. 3. To provide biostatistical support for the gene expression studies performed by Core C in support of the Projects.